Friday, 28 February 2025 11:00am – 12:00pm

This seminar will be delivered in Chemistry Lecture Theatre 4

Speaker: Dr Charles Bayly-Jones

Host: A/Prof. Ron Clarke

Title: Plant tropisms may be key to putting cancer on a diet

Abstract: Lysosomes play crucial roles in regulating our cellular metabolism. However, these tiny compartments do more than just break things down – they also help cells adapt to their environment. Where mitochondria are “the powerhouse of the cell”, lysosomes can be thought of as the “signal control centre”. Lysosomes monitor changes in nutrient and energy availability and subsequently trigger cellular responses, thus controlling cell growth. These control mechanisms are fundamentally conserved from yeast, to worm, to human and must be strictly obeyed by the cellular machinery. Dysregulation of this pathway is implicated in diseases ranging from cancer, to metabolic syndromes, to neurological disorders.

One key player in this process is a protein called LYCHOS. Lysosomal sensing pathways consist of many sensors, triggers, and signalling molecules.  LYCHOS is, however, the only known sensor that can monitor cholesterol in the AKT/mTOR pathway. This intriguing protein was discovered mid-2022, but how LYCHOS detects cholesterol and influences cell growth was an open question.

Using several advanced imaging techniques, we determined the structure of LYCHOS and revealed a surprising commonality to plant hormone transporters (Bayly-Jones et al, Nature 2024). We demonstrate that LYCHOS is a hybrid molecule consisting of both a G protein-coupled receptor and a plant transporter. Hence, it is the only mammalian member of the previously exclusively plant transporter family. By repurposing plant machinery, evolution has forged a novel and intriguing mammalian cholesterol sensor. In this lecture I will show how this research connects cholesterol, a strictly animal molecule, to plant growth. How plant hormone signalling may affect G protein signalling. How nature is lazy, reusing biological machines in unexpected ways, and finally, why it matters for human health.

Bio: Charles Bayly-Jones completed his bachelor’s degree (2016; BSc Science Scholar program) at Monash University with specialisations in theoretical physics and biochemistry. He continued his studies at Monash and earned a PhD (2021) training within the ARC Centre of Excellence for Advanced Molecular Imaging. He was a post-doctoral researcher under the mentorship of ARC laureate fellow Professor James Whisstock (2021-2022), before joining the group of Associate Professor Andrew Ellisdon (2023-current). Charles oversees an emerging team of his own at the Biomedicine Discovery Institute. Here, Charles has established a research program around single-molecule methods to probe protein conformational dynamics. To this end, he uses integrative structural biology approaches (cryoEM, X-ray crystallography, biosensors) to study complex nanomolecular machines. Charles developed the software package “WIGGLE” and is currently building software and biotechnologies to accelerate discovery science in the TSC/mTORC1 field. He has successfully led several projects at both the national and international level, bridging academia and industry. He currently holds an NHMRC Ideas grant in collaboration with A/Prof Ellisdon and Monash Medicine Early Career Research Excellence Program funding. He is an ARC DECRA fellow.